Microbial transformation studies are being conducted with highly active antitumor conpounds isolated from natural sources. Microorganisms are used to accomplish selective chemical changes in the structures of such chemicals under the mild reaction conditions obtained in fermentations. Where appropriate, derivatives of microbial metabolites will be prepared and tested in suitable tumor test systems. Our efforts are intended to continue the development of microorganisms as tools to prepare quantities of potentially active antitumor drug metabolites; to elucidate new and possibly important pathways of metabolism of structurally complicated antitumor compounds; and to provide difficult-to-synthesize drug metabolites for biological testing, and for structure elucidation work. All of these studies facilitate our understanding of mammalian metabolic transformations of the same kinds of antitumor compounds. Experiments are currently being pursued with the Vinca alkaloids, d-tetrandrine, podophyllotoxin derivatives, diterpenes and others. Structures of obtained microbial metabolites are determined by chemical and spectral methods, and they will be examined for antitumor activity.